The present invention relates to controlled release unit dose formulations of diltiazem hydrochloride (diltiazem). Diltiazem is sold commercially in extended release pharmaceutical dosage forms in order to maintain a therapeutic serum level of diltiazem and to minimize the effects of missed doses of drugs caused by a lack of patient compliance. The minimum therapeutic plasma diltiazem concentrations are in the range of 50 to 200 ng/ml.
In the prior art extended release formulations of diltiazem tablets have been marketed which provide 24 hour therapeutic blood levels of diltiazem with once a day administration of a single dosage unit. Cardizem.RTM. CD is described as a once-a-day extended release capsule containing diltiazem and fumaric acid. In the file history of U.S. Pat. No. 5,286,497, representations were made that the formulation disclosed in that patent is the formulation for Caridizem.RTM. CD. The formulation for Cardizem.RTM. CD is identified in the file history of U.S. Pat. No. 5,286,497 as having a "stair-step release profile" which has a rapid release bead and an extended release bead.
The other commercially available diltiazem once-a-day formulation is sold under the Dilacor XR.RTM. trademark. This formulation is described as being based on the Geomatrix" controlled release system which is described in U.S. Pat. No. 4,839,177.
In U.S. Pat. No. 5,229,135, a once-a-day formulation is described that is based on a single pellet which is prepared with an active core which is coated with diltiazem and an inner and outer membrane.
Other diltiazem formulations are disclosed in U.S. Pat. No. 4,721,619; U.S. Pat. No. 4,894,240; U.S. Pat. No. 5,002,776; U.S. Pat. No. 5,364,620; U.S. Pat. No. 4,891,230; U.S. Pat. No. 4,917,899; U.S. Pat. No. 5,288,505; and U.S. Pat. No. 5,336,504.
The present invention provides a novel diltiazem once-a-day formulation two-pellet based capsule formulation which does not have a "stair-step release profile" and does not require the presence of fumaric acid or any other organic acid.